tbuckley/cabot-search huggingface dataset:
A single-institution, retrospective examination of new contrast enhancement, progression, and pseudoprogression in <i>IDH </i>mutant glioma.
Authors: Ethan Wetzel, Blaine S.C. Eldred, Vicki Liu, Serendipity Zapanta Rinonos, Negar Khanlou, Linda M. Liau, Phioanh Leia Nghiemphu, Timothy Francis Cloughesy, Benjamin M. Ellingson, Albert Lai
Journal: Journal of Clinical Oncology (2022)

2043 Background: IDH mutant glioma patients are followed by MRI, where new contrast enhancement (CEnew) is a hallmark of tumor progression. Interpretation of CEnew is confounded by pseudoprogression (PsP), the appearance of CEnew that spontaneously resolves on subsequent scans. PsP has been characterized in IDH wildtype patients, but is poorly understood in the IDH mutant category. This study represents an examination of the characteristics and impacts on patient survival of CEnew in IDH mutant gliomas. Methods: Of the 724 confirmed IDH mutant glioma patients treated at UCLA between 1998 and 2022, 587 were included (median follow-up = 5.23 years). Patients were excluded based on these criteria: &lt;4 MRI scans, unknown IDH status, and unknown WHO 2016 diagnosis. CEnew was first identified by direct review of images and confirmed by the radiology report. Any new enhancement appearing on the first post surgical MRI was not considered CEnew. CEnew was interpreted as progression after surgical resection indicating tumor or the re-initiation of chemotherapy or radiation and was considered PsP after the resolution of enhancement without new treatment initiation. Some PsP patients could have received bevacizumab. Kaplan-Meier survival analyses were used to examine overall survival differences between groups. Results: 327 of 587 patients developed CEnew. The incidence of CEnew was higher in Grade 4 Astrocytoma (G4 Astro) versus all other pathologies and lowest in LO (p &lt; 0.05). The Enhancement Free Survival (EFS) was shortest for G4 Astro patients (p =.002); LO patients had the longest median EFS of 2602 days (p = 0.002). The development of CEnew and presence of preoperative enhancement were both found to be negative survival prognosticators in all pathologies (p &lt; 0.05). From our analysis, 92 patients developed PsP and 177 developed progression. The median duration of a PsP spot was 244 days. PsP spots appeared earlier than progression spots (median 538 vs 1113 days, p =.001). The incidence of PsP was highest in the G4 Astro group and lowest in LO patients. Survival analysis of patients with progression versus those with PsP and progression shows PsP is associated with longer OS in the entire cohort and the LO, AO, AA, and G4 Astro groups (p &lt; 0.05). 100% of PsP patients received radiation therapy (RT). The median time from the end of RT to PsP was 209 days. Conclusions: While CEnew in IDH mutant gliomas is associated with reduced OS, poorer outcome is driven by progressors. PsP represents 28% of CEnew instances, typically occurs within 1 year of RT and have superior outcome to progressors and equivalent to of patients that do not display CEnew. [Table: see text]
Cytokine profile in peripheral blood of patients with metastatic colorectal cancer with different responses to chemotherapy in combination with anti-VEGF agents.
Authors: Liubov Yu Vladimirova, Aleksandr B. Sagakyants, Anna V. Tishina, Oksana G. Shulgina, Anna E. Storozhakova, Ekaterina I. Zolotareva, Inna A. Novikova, Elena A. Kalabanova, Sergey N. Kabanov, Natalia Yu. Samaneva, Maria A. Teplyakova, Natalia M. Tikhanovskaya, Natalia A. Abramova, Irina A. Udalenkova, Ludmila A. Ryadinskaya, Irina L. Popova, Marina M. Sergeeva, Oleg I. Kit, Elena A. Dzhenkova, Evgeniy N. Kolesnikov
Journal: Journal of Clinical Oncology (2022)

e15545 Background: For many years, colorectal cancer has been among the most frequently diagnosed cancers and one of the leading causes of cancer death. The effect of monoclonal antibodies on the immunological status remains relevant, since chemotherapy in combination with monoclonal antibodies (anti-EGFR, anti-VEGF) plays a key role in the treatment of patients with metastatic colorectal cancer. The purpose of this study was to reveal specific features of the cytokine profile of patients with metastatic colorectal cancer (mCRC) receiving bevacizumab in combination with chemotherapy before and after the treatment. Methods: The study included 15 patients with newly diagnosed mCRC receiving mFOLFOX6 chemotherapy combined with bevacizumab as the first-line treatment. Cytokine levels were determined in the blood serum (BS) by multiplex assay with the Bio-Plex Pro Human Immunotherapy 20-Plex Panel (GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17A, IL-18, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, TNF-α) (Bio-Rad, USA) before and after 4 cycles of the therapy. Results were evaluated using the Luminex 200 Analyzer (Bio-Rad, USA) with the Bio-Plex Manager Software. Results: Complete response to the therapy was registered in 5 (33.3%) patients, partial remission in 8 (53.3%) patients, progression in 13.3%. IL-6, IP-10, MIG, RANTES, and TNF-a were statistically significantly (p &lt; 0.05) elevated in patients with complete response. IL-8 showed a tendency to decreasing after the therapy. Levels of IL-6, IL-8, IL-15, IL-17, and MIP-1a in patients with partial remission after the therapy reduced to zero values. An analysis of the cytokine profiles in patients with progression demonstrated a decrease of all the studied indices, except for elevated IL-15 and IL-17. Conclusions: Anti-VEGF agents together with chemotherapy changed the cytokine profiles in patients with mCRC. Probable mechanism may include the implementation of the antitumor response through the activation of some pro-inflammatory cytokines, since the complete response was accompanied by an increase in IL-6, IP-10, MIG, RANTES, TNF-a and a decrease in IL8.
The efficacy of afatinib combined with bevacizumab in first-line treatment of EGFR-mutated advanced non-small cell lung cancer.
Authors: Yangli Liu, Haihong Chen, Wei Liang, Yukun Kuang, Yubiao Guo, Ke-Jing Tang
Journal: Journal of Clinical Oncology (2022)

e21124 Background: The addition of bevacizumab to first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) has shown promising efficacy in delaying TKI resistance and prolonging PFS in treating EGFR-mutated advanced lung cancer. However, data on the afatinib-bevacizumab combination therapy are limited. Methods: A total of 47 patients with EGFR-mutated advanced lung cancer were retrospectively analyzed, including 21 patients treated with afatinib combined with bevacizumab and 26 patients treated with afatinib monotherapy. Clinical data, survival outcomes and toxic effects were evaluated. Results: There was no significant difference in basic clinical features between the combination and monotherapy groups. The overall response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the combination group (afatinib 40 mg/day combined with bevacizumab 7.5 mg/kg every 3 weeks) were 42.9%, 16.5 months and 35.2 months, respectively, while the ORR, PFS and OS in the afatinib group was 53.8%, 13.8 months and 33.8 months, respectively. No significant difference was noted in ORR, PFS or OS between the two groups ( p＞0.05). However, among the subgroup with concurrent genetic mutations, combination therapy provided a significant PFS benefit (18.2 months, [95% CI 7.1-29.3] vs. 11.0 months [95%CI 7.5-14.5], p= 0.036). Although there was a longer trend in OS, no statistical difference was presented (35.2 months [95% CI 29.8-40.6] vs. 27.5 months [95% CI 13.1-41.9], p= 0.138). The safety of the combination therapy was acceptable and manageable. Conclusions: Afatinib-bevacizumab combination therapy could provide superior PFS benefit over afatinib alone in the subset of patients with concomitant genetic mutations in EGFR-mutated advanced NSCLC, and the safety of the combination therapy is acceptable.[Table: see text]
Remote geriatric assessment program for older patients starting new chemotherapy treatment in Brazil.
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Marianne Razavi, Sabri Lakhdari, Errol James Philip, Marcos V S Franca, Lorena Nascimento Manrique Molina, Alici Natalia de Sousa Freitas, Mariane Cunha Taveira, Andressa Cardoso Azeredo, William Hiromi Fuzita, Cristiano Menezes Fernandes, Raquel Baptista Pio, Romildo De Araujo Periera Filho, Milena Macedo Couto, Vitor Fiorin de Vasconcellos, Joao Nunes Matos Neto, Marco Murilo Buso, Enrique Soto Pérez de Celis, William Dale
Journal: Journal of Clinical Oncology (2022)

12052 Background: Older cancer patients in developing countries face considerable challenges in obtaining access to specialized medical attention, often due to a lack of human resources and healthcare infrastructure. This study sought to explore the benefit of a remote, validated geriatric assessment (GA) program for older patients starting chemotherapy in Brazil. Methods: Older adults (65+ years) beginning a new chemotherapy treatment regimen in Brazil were recruited. Through telehealth, patients were assessed with GA before starting chemotherapy treatment for any type of solid cancer and at a follow-up visit (3 months after enrollment). GA results were discussed by a multidisciplinary team (e.g., geriatrician, psychologist, nutritionist) and recommendations were determined. Outcome measures included chemo toxicity scores (CARG, scale 0-19), physical symptoms (FACT-G, scale 0-108) and activities of daily living (IADL, scale 0-5 for men and 0-8 for women, or scale 0-1 for IADL ratio). Descriptive statistics were generated, and paired t-tests were used to evaluate the change in these measures over time. Results: A total of 51 older patients from 5 different Brazilian states (Amazonas, Distrito Federal, Espirito Santo, Pernambuco and Rio Grande do Sul) have been enrolled to date. The mean distance from a patients’ home to their place of cancer treatment was 21 miles (range: 3-101 miles). Participants had a mean age of 76.5 years (SD = 7.6) and were predominantly female (57%), white (57%), married (61%), and had a high school degree or more (65%). Patients were mostly diagnosed with gastrointestinal (39%) or gynecological (20%) cancers; 55% of patients were diagnosed with a stage IV disease. The majority of patients (80%) were referred to appropriate remote services based on the GA; including geriatricians (41%), nutritionists (39%) and/or psychologist (16%). At the time of abstract submission, data from 34 complete cases were available for longitudinal analysis, in which we observed a decrease in chemo toxicity scores (M 1 = 6.65, M 2 = 5.88, p = 0.035) and an improvement in FACTG (M 1 = 92.94, M 2 = 98.53, p &lt; 0.001). The improvement in IADL ratio was not significant (M 1 = 0.79, M 2 = 0.85, p = 0.069). Conclusions: This novel, ongoing study is, to our knowledge, the first to implement a remote GA program in Brazil. Our preliminary findings suggest that a remote GA program, with appropriate referrals to specialists, may increase the reach of supportive services and improve cancer care in developing countries.
Sacubitril-valsartan improves longitudinal strain and ejection fraction in preclinical models treated with anthracyclines through NLRP3, MyD88 pathways resulting in a reduction of myocardial IL-1β, IL-6, TNF-α and growth factors.
Authors: Nicola Maurea, Martina Iovine, Simona Buccolo, Antonietta Caronna, Carlo Maurea, Annamaria Bonelli, Andrea Paccone, Irma Bisceglia, Maria Laura Canale, Vincenzo Quagliariello
Journal: Journal of Clinical Oncology (2022)

12063 Background: Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction. We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function and cardiac inflammation in preclinical models. Methods: Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: cell viability, apoptosis and necrosis; expression of malondialdehyde and 4-hydroxynonenal and concentration of intracellular Ca2+. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; NF-κB). C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n = 6), LCZ-696 at 60 mg/kg (LCZ, n = 6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n = 6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, NF-kB and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. Results: LCZ-696 exerts cardioprotective effects, enhancing cell viability of 48-54.6% compared to only doxorubicin-treated cells (p &lt; 0,001 for all); LCZ 696 decreased NLRP3, MyD88 and NF-kB expression in cardiac cells. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88 and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p &lt; 0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties. Conclusions: LCZ-696 exerts direct beneficial effects in cardiomyocytes exposed to doxorubicin. In preclinical models, LCZ-696 reduced inflammation and cytokine expression involved in doxorubicin-mediated cardiotoxicity.
Retrospective analysis of the effect of angiotensin receptor blockers and angiotensin converting enzyme inhibitors on the efficacy of anti-PD-1/PD-L1 immunotherapy in patients with advanced cancer.
Authors: Jason Suh, John R. Rutledge, Philip Adam Friedlander
Journal: Journal of Clinical Oncology (2022)

2605 Background: Components of the renin angiotensin system (RAS) are expressed in tumors with activation leading to tumor and stromal cell release of immunomodulatory cytokines promoting an immunosuppressive microenvironment and increased infiltration of tumor associated macrophages. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are anti-hypertensives that inhibit the RAS. It is unknown if ACEi and ARB treatment modulates the efficacy of anti-PD-1/PD-L1 immunotherapy. Methods: A retrospective chart review was conducted to identify patients with unresectable malignancies initiating treatment with a PD-1 or PD-L1 inhibitor based regimen between 1/1/13 and 6/1/19 at Valley Hospital in New Jersey. IRB approval was obtained. Efficacy of treatment was measured by medical oncologist documentation of clinical benefit (CB = stable disease / treatment response) versus disease progression. Chi-square tests were performed to assess relationship between ACEi or ARB exposure and immunotherapy benefit. To assess for a broader anti-hypertensive effect, the relationship in patients on a beta-blocker but not ACEi/ARB was assessed. Results: 197 patients were identified of which 190 had documentation of clinical outcome. The mean age was 72.8 years with 54% female and 46% male. 56 patients were exposed to ACEi (N = 28) or ARB (N = 28) and 141 patients to neither. 37 patients were exposed to beta blocker but not ACEi or ARB. 60 patients had nonsquamous NSCLC (16 on ACEi or ARB), 26 squamous NSCLC (7 on ACEi or ARB) and 24 melanoma (10 on ACEi or ARB). 71% of ACEi/ARB exposed patients had CB by clinician assessment as opposed to 47% in those not on ACEi or ARB (p = 0.003). In ACEi exposed patients, 71% had CB versus 51% in unexposed patients (p = 0.048). In ARB exposed patients, 70% had CB versus 51% in unexposed patients (p = 0.069). By contrast, 51% of beta-blocker treated patients had CB versus 55% in untreated patients (p = 0.72). 36% of ACEi/ARB exposed patients remained on treatment at 12 months versus 22% of ACEi/ARB unexposed patients. Subset analyses were performed on the 3 largest patient populations: squamous NSCLC, nonsquamous NSCLC and melanoma. ACEi/ARB exposed melanoma patients had CB rate of 70% versus 43% in those unexposed. ACEi/ARB exposed squamous NSCLC patients had CB rate of 86% versus 47% in unexposed patients. By contrast, ACEi/ARB exposed nonsquamous NSCLC patients had a 56% CB rate versus 48% in unexposed patients. Conclusions: Based on retrospective analysis, advanced cancer patients treated with anti-PD-1/PD-L1 regimens had a statistically significant increase in clinical benefit if administered in the context of renin angiotensin system blockade. Prospective disease specific trials can further validate these findings and define the degree of clinical benefit.
The effects of AVM0703 mobilization of endogenous gamma delta/invariant TCR+ bispecific natural killer T-like cells against solid tumors and blood cancers.
Authors: Theresa Deisher, Janet R. Rea, Peter Jarzyna, Kendra Poulin, Yumna Zahid, Vaishnavi Parthasarathy, Spencer Sawas, Manisha Pathak, Stephanie Lee-Diaz, Kathleen Suwito, Colleen Rylatt
Journal: Journal of Clinical Oncology (2022)

2579 Background: Glucocorticoids (GC) are a common component of blood cancer regimens, typically at doses 40 mg or lower due to concerns of pancreatitis and hepatotoxicity (Walasik-Szemplińska et al. Thyroid Research. 2019;12:13; Ataallah et al. Cureus. 2020;12[7]) and neuropsychiatric effects. AVM Biotechnology has developed a high concentration, high volume, preservative-free, patent pending formulation of dexamethasone (AVM0703), that allows administration of up to 21 mg/kg (1470 mg for 70 kg) over a one-hour IV infusion. Prophylactic use of circadian physiologic hydrocortisone reduces the risk of GC neuropsychiatric side-effects (Warris LT, et al. J. Clin. Oncol. 2016;34:2287; Meijer &amp; de Kloet Endocrinology. 2017;158:448). Acute supra-pharmacologic doses (&gt;6 mg/kg) AVM0703 mobilizes endogenous bispecific gamma delta invariant TCR+ bi-specific Natural Killer T-like cells (AVM-NKT) (PCT/US21/19773), via a non-GC receptor, that rapidly home to diseased organs in preclinical models and are directly related to tumor killing, including Non-Hodgkin’s Lymphoma, Melanoma, and Multiple Myeloma. Methods: Cancer cell lines and (mouse host) were i) immune-resistant mouse A20 B lymphoma (Balb/c), ii) xenografted human T-ALL CCRF-CEM (NCRnu), iii) mouse B16F10 melanoma (B62DF1), and iv) mouse MOPC315 (Balb/c). Cancer cell lines were inoculated into the flank either as single cell suspensions or encased in Matrigel. When tumor volume reached between 100-500mm 3 well-established tumors, mice were orally gavaged with a human equivalent dose (HED) of 15-18 mg/kg AVM0703 as monotherapy, or as a preconditioning prior to adoptive cell transfer (ACT), or in combination with chemotherapy. Responses were determined by tumor volume measurements, tumor immunohistochemistry or flow cytometry detection of residual cancer cells. Results: Immunohistochemistry analysis of tumors from AVM0703 treated mice demonstrated pseudoprogression similar to checkpoint inhibitors: i.e. tumors were measurable however in some cases all cancer cells had been eradicated. Therefore, subsequent tumor monitoring at end point was done by flow cytometry to quantify the total number of live cancer cells more accurately than tumor measurements by calipers or immunohistochemistry, due to pseudoprogression and limitations of examining only a few sections from each tumor. Conclusions: AVM0703 led to: i) complete response (CR) in 27% of immune-resistant mouse A20 tumors as monotherapy and CR in 60% when combined with 2 doses of cyclophosphamide/fludarabine (CyFlu); ii) tumor eradication and long-term memory against xenografted human T-ALL; iii) enhancement of ACT equivalent to CyFlu preconditioning in mouse melanoma; and iv) preliminary 95% CR against mouse multiple myeloma.
Oncologist consideration of patient health insurance coverage and out-of-pocket costs for genomic testing in treatment decision.
Authors: Kewei Shi, K. Robin Yabroff, Jingxuan Zhao, Janet De Moor, Andrew Freedman, Zhiyuan Zheng, Leticia M. Nogueira, Xuesong Han, Carrie N. Klabunde
Journal: Journal of Clinical Oncology (2022)

6600 Background: Use of genomic testing, especially multi-marker tumor panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Although most patients are concerned about OOP costs, little is known about oncologists’ treatment decisions with respect to patient health insurance coverage and OOP costs for genomic testing. Methods: We identified 1,049 oncologists who reported using multi-marker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regression analyses were used to assess the associations of oncologist, practice, and patient characteristics and the oncologist ratings of the importance of health insurance coverage and OOP cost for genomic testing as part of treatment decisions. Results: Among oncologists, 47.3%, 32.7% and 20.0% reported that patient insurance coverage for genomic testing was very important, somewhat important, and a little/not important, respectively, in treatment decisions. 56.9%, 28.0%, and 15.2% reported patient OOP costs for genomic testing were very, somewhat, or a little/not important in treatment decisions, respectively. In adjusted ordinal logistic regression analyses, oncologists who used next-generation gene sequencing tests were more likely to report patient health insurance and OOP costs for testing as important (odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.2, 3.5) and (OR = 2.1; 95%CI: 1.2, 3.7), respectively) in treatment decisions. Oncologists with more years of experience, who treated solid tumors (rather than only hematological cancers), worked in practices without molecular tumor boards for genomic tests, and with higher percentages of patients insured by Medicaid or self-paid/uninsured also reported insurance coverage or OOP costs for testing were important in treatment decisions (all p &lt; 0.05). Conclusions: Physician, practice, and patient characteristics were associated with oncologists’ ratings of the importance of patient health insurance and OOP costs in treatment decisions. Identifying factors that influence physicians’ priorities in treatment decisions may inform the development and targeting of interventions to support patient and physician discussions about oncology care.